tbuckley/cabot-search huggingface dataset:
Investigations into the Effect of Hot, Dry Microclimate on Peripheral Circulation, etc., in Arthritic Patients
Authors: G. Edstrom, G. Lundin, T. Wramner
Journal: Annals of the Rheumatic Diseases (1948)

During the last six years one of the wards of the University Hospital in Lund has been used as a climatic laboratory.The temperature of the air in the room can be adjusted between what is normal outdoor temperature in south Sweden-in the winter below zero-and 400 C., the relative humidity be- tween 30 per cent.and complete saturation, and both these factors can be kept constant at the level desired with a very small range of variation.registration of the electromotive power a multiflex galvanometer was used, so graduated that every line on the scale corresponded to 0.05°C., which was controlled by repeated calibrations.When measurements were 76
Intestinal Lipodystrophy (Whipple's Disease)
Authors: Julian M. Ruffin
Journal: JAMA (1966)

It is now generally accepted that the treatment of choice for intestinal lipodystrophy (Whipple's disease) is antibiotic therapy.<sup>1-5</sup>At one time, it was thought that steroids were of value, and clinical recoveries after their administration have been reported.<sup>6</sup>However, the widespread use of antibiotics in febrile illness and in preoperative and postoperative management makes it difficult to conclude that those patients who recovered after the use of steroids did not also receive antibiotics at some time during the course of their disease.<sup>2</sup>Furthermore, recurrences after therapy are common,<sup>1,7</sup>and, unless the case has been followed for a considerable period, it is difficult to evaluate the long-term effect of treatment. To determine the immediate and the prolonged effect of antibiotic therapy in intestinal lipodystrophy, a review was undertaken of ten patients so treated at Duke University Medical Center during the past 15 years. <h3>Materials and Methods</h3> Sixteen
Toxicity Following Methoxyflurane Anesthesia
Authors: Bernard J. Panner
Journal: JAMA (1970)

Two patients who received methoxyflurane anesthesia during abdominal surgery developed polyuric renal failure within 24 hours after their operations. Both patients died after complicated clinical courses which were dominated by renal failure. Toxic effects to the kidneys suspected of being related to methoxyflurane were characterized by polyuria and progressive azotemia. Postmortem examination in both cases revealed crystals resembling calcium oxalate in renal tubules. The possibility of concurrent toxic effects to the liver is also considered.
Pulmonary hypertension after transjugular intrahepatic portosystemic shunt: Effects on right ventricular function
Authors: P Van der Linden, O Le Moine, M Ghysels, M Ortinez, J Deviere
Journal: Hepatology (1996)

The short- and mid-term hemodynamic effects of transjugular intrahepatic portosystemic shunt (TIPS) were studied in 16 sedated cirrhotic patients. Indications included relapsing variceal bleeding (n = 10) and refractory ascites (n = 6). The decrease of porto-atrial pressure gradient (from 20.4 ± 4.2 mm Hg to 10.1 ± 2.4 mmHg; P &lt; .05) was associated with an increase of mean pulmonary artery pressure (MPAP) (from 12.3 ± 3.0 mm Hg to 20.3 ± 5.3 mm Hg; P &lt; .05) and of right atrial pressure (RAP) from 3.4 ± 2.6 mm Hg to 8.3 ± 3.7 mm Hg; P &lt; .05), whereas right ventricular end-diastolic volume (RVEDVI) remained unchanged. The significant increase of cardiac index (CI) (from 4.5 ± 1.2 L/min/m 2 to 5.0 ± 1.1 L/min/m 2 ; P &lt; .05) was essentially attributable to an increase of heart rate (HR) (from 81 ± 11 to 88 ± 10 beats/min; P &lt; .05). Systemic vascular resistance (SVR) decreased (from 812 ± 281 to 666 ± 191 dynes/sec/cm 5 ; P &lt; .05), whereas pulmonary vascular resistance (PVR) increased (from 60.6 ± 29.6 to 82.0 ± 34.6 dynes/sec/cm5; P &lt; .05). After transient shunt occlusion with a balloon catheter, all of the hemodynamic parameters returned to baseline values, except pulmonary artery pressure, which also decreased but remained significantly increased. One month after TIPS, pulmonary pressure remained elevated, and CI further increased. It is concluded that increased PVR is the major hemodynamic alteration occurring after TIPS placement. It correlates with the decrease of porto-atrial gradient and is probably mediated by both mechanical and neurohumoral factors.
The Similarity and Frequency of Proposals to Reform US Medical Education
Authors: Nicholas A. Christakis
Journal: JAMA (1995)

<h3>Objectives.</h3> —To identify the values and agendas underlying reports advocating the reform of medical education and to account for their similarity and repeated promulgation. <h3>Data Sources.</h3> —Major reports regarding undergraduate medical education reform published between 1910 and 1993 were identified through a manual bibliographic search. <h3>Study Selection.</h3> —Nineteen of a total of 24 reports met the two inclusion criteria: they directly addressed undergraduate medical education and contained a coherent body of recommendations. <h3>Data Extraction.</h3> —Content analysis of 19 reports. <h3>Data Synthesis.</h3> —All the reports articulate a specifically social vision of the medical profession, in which medical schools are seen as serving society. The reports are remarkably consistent regarding the objectives of reform and the specific reforms proposed. Core objectives of reform include the following: (1) to better serve the public interest, (2) to address physician workforce needs, (3) to cope with burgeoning medical knowledge, and (4) to increase the emphasis on generalism. Proposed reforms have tended to suggest changes in manner of teaching, content of teaching, faculty development, and organizational factors. Reforms such as increasing generalist training, increasing ambulatory care exposure, providing social science courses, teaching lifelong and self-learning skills, rewarding teaching, clarifying the school mission, and centralizing curriculum control have appeared almost continuously since 1910. <h3>Conclusion.</h3> —The similarity of the reports' objectives and reforms results not only from a similar body of problems, but also from the reaffirmation of similar values. The reports have two implicit agendas that transcend the reform of medical education: the affirmation of the social nature of the medical profession and self-regulation of the profession. These agendas help account for the reports' similarity and their repeated promulgation. (<i>JAMA</i>. 1995;274:706-711)
Improvements in Burn Care, 1965 to 1979
Authors: Irving Feller
Journal: JAMA (1980)

Data from the National Burn Information Exchange indicate that the quality of burn care in the United States is improving in the participating health care facilities. Case reports of 37,442 patients collected between 1965 and 1979 from 120 burn care facilities have been examined. These data show that overall survival rates are increasing and hospitalization times are decreasing at all levels of burn severity. The changes are associated with a trend toward more timely wound closure for full-thickness burns and are evident in the majority of hospitals studied. Tables of current survival rates and hospitalization times, by patient age and size of burn, are presented. (<i>JAMA</i>244:2074-2078, 1980)
Valsartan for Prevention of Recurrent Atrial Fibrillation
Authors: The GISSI-AF Investigators
Journal: New England Journal of Medicine (2009)

Atrial fibrillation is the most common cardiac arrhythmia, and no current therapy is ideal for control of this condition. Experimental studies suggest that angiotensin II–receptor blockers (ARBs) can influence atrial remodeling, and some clinical studies suggest that they may prevent atrial fibrillation.
Association of the Missense Glu298Asp Variant of the Endothelial Nitric Oxide Synthase Gene With Myocardial Infarction
Authors: Yukio Shimasaki, Hirofumi Yasue, Michihiro Yoshimura, Masafumi Nakayama, Kiyotaka Kugiyama, Hisao Ogawa, Eisaku Harada, Takenobu Masuda, Wasaku Koyama, Yoshihiko Saito, Yoshihiro Miyamoto, Yoshihiro Ogawa, Kazuwa Nakao
Journal: Journal of the American College of Cardiology (1998)
CHARACTERIZATION OF THE CLASS I HLA 9.2‐kb <i>PVU</i> II RESTRICTION FRAGMENT LENGTH POLYMORPHISM: Linkage to HLA‐A and Lack of Disease Association
Authors: Joseph M. Ahearn, Jon J. Calomiris, Fredrick M. Wigley, Douglas A. Jabs, Wilma B. Bias, Marc C. Hochberg
Journal: Arthritis & Rheumatology (1989)

The strongest reported association between a class I HLA allele and disease is that of HLA–B27 with ankylosing spondylitis (AS). However, it has not been shown whether B27 is the gene that predisposes to the development of AS or if it is merely linked with the disease‐susceptibility locus. Furthermore, if B27 itself is the disease‐susceptibility gene, there may be epistatic loci that also contribute to the development of AS or modify its clinical manifestation. A class I HLA 9.2‐kb Pvu II restriction fragment was recently identified, which, when present in a B27‐positive individual, further increased the relative risk for developing AS (from 119 to 297). This study was therefore designed to confirm the association between AS and this restriction fragment length polymorphism (RFLP) and to map the location of this fragment in the genome. The data presented here suggest that the class I HLA 9.2‐kb Pvu II RFLP represents a Pvu II polymorphism at the 5' end of the HLA–A locus that is tightly linked with both HLA–A3 and A9 alleles. However, there is no association between this RFLP and AS in a population of patients living in Baltimore.
SENSITIVITY OF A HEALTH STATUS MEASURE TO SHORT‐TERM CLINICAL CHANGES IN ARTHRITIS
Authors: Jennifer J. Anderson, Hill E. Firschein, Robert F. Meenan
Journal: Arthritis & Rheumatology (1989)

To assess the sensitivity of the Arthritis Impact Measurement Scales (AIMS), we analyzed data from 3 clinical trials. One trial involving 255 patients with rheumatoid arthritis (RA) was a 12‐week, randomized controlled trial of diclofenac, naproxen, and aspirin. Two trials were open‐label studies of 24 weeks duration that included 165 RA and 355 osteoarthritis (OA) patients, all of whom were treated with diclofenac. In addition to the AIMS, tender joint count, morning stiffness, and erythrocyte sedimentation rate were used as outcome measures in the trials. The AIMS results showed substantial improvements in Physical Function, Psychological Status, and Pain, as well as in overall Arthritis Impact. These improvements were detected by the time of the initial outcome assessment at 4 weeks or 8 weeks, and were detected in patients with either OA or RA. These AIMS results closely parallel improvements shown by traditional clinical measures, and demonstrate that the AIMS health status measure is sensitive to improvements in OA as well as in RA. The AIMS also detects responses produced by therapy with nonsteroidal antiinflammatory drugs (NSAIDs), and these improvements can be demonstrated in as short a treatment time as 4 weeks. These findings confirm the utility of the AIMS for assessing outcome in rheumatic disease studies, and they have implications for the design of future clinical trials of NSAIDs.
ANTIBODIES TO HISTONES H1 AND H5 IN SERA OF PATIENTS WITH JUVENILE RHEUMATOID ARTHRITIS
Authors: John D. Pauls, Earl Silverman, Ronald M. Laxer, Marvin J. Fritzler
Journal: Arthritis & Rheumatology (1989)

The specificity of juvenile rheumatoid arthritis (JRA) sera for histone subclasses was examined by immunoblotting. Antibodies to H1 alone were found in 4 of 21 pauciarticular‐onset JRA sera, 4 of 19 polyarticular‐onset JRA sera, and 2 of 11 systemic‐onset JRA sera. Antibodies to H5 alone were found in 1 of 21 pauciarticular JRA sera, 1 of 19 polyarticular JRA sera, and 3 of 11 systemic JRA sera. Antibodies to both H1 and H5 were found in 4 of 21 pauciarticular JRA sera, 4 of 19 polyarticular JRA sera, and 1 of 11 systemic JRA sera. Antibodies to the core histones (H2A and H2B) were found in 1 of 21 pauciarticular JRA sera, 1 of 19 polyarticular JRA sera, and no systemic JRA sera. No reactivity to histones was observed in 30 sera from age‐matched children with nonrheumatic diseases. The presence of H1 and H5 antibodies did not correlate with antinuclear antibody titers or with a homogeneous pattern of immunofluorescence. The predominance of H1 and H5 antibodies and relative absence of antibodies binding to core histones in JRA contrast with findings in adult systemic lupus erythematosus. Further, the presence of antibodies to H5 alone in some of the JRA patients indicates that the immune response in these patients is directed to determinants that are not shared by sequences of mammalian proteins.
Anti-Amyloid Monoclonal Antibodies are Transformative Treatments that Redefine Alzheimer's Disease Therapeutics
Authors: Jeffrey Cummings
Journal: Drugs (2023)

Two anti-amyloid monoclonal antibodies (MABs)—lecanemab (Leqembi®) and aducanumab (Aduhelm®)—have been approved in the USA for the treatment of Alzheimer's disease (AD). Anti-amyloid monoclonal antibodies are the first disease-modifying therapies for AD that achieve slowing of clinical decline by intervening in the basic biological processes of the disease. These are breakthrough agents that can slow the inevitable progression of AD into more severe cognitive impairment. The results of trials of anti-amyloid MABs support the amyloid hypothesis and amyloid as a target for AD drug development. The success of MABs reflects a relentless application of neuroscience knowledge to solving major challenges facing humankind. The success of these transformative agents will foster the development of more anti-amyloid MABs, other types of anti-amyloid therapies, treatments of other targets of AD biology, and new approaches to therapies for an array of neurodegenerative disorders. Monoclonal antibodies have side effects and, during the period of treatment initiation, patients must be closely monitored for the occurrence of amyloid-related imaging abnormalities (ARIA) and infusion reactions. A successful first step in the development of disease-modifying therapy for AD defines desirable features for the next phase of therapeutic development including less frequent ARIA, more convenient administration, and greater efficacy. Unprecedented agents make new demands on patients and care partners, clinicians, payers, and health care systems. Collaboration among stakeholders is essential to take advantage of the therapeutic benefits offered by these agents and to make them widely available. Monoclonal antibodies usher in a new era in AD therapy and define a new landscape of what is possible for therapeutic development for neurodegenerative disorders.
Affinity matters for <scp>IgE</scp>‐blocking activity of allergen‐specific antibodies
Authors: Maria R. Strobl, Hilal Demir, Gerhard Stadlmayr, Florian Stracke, Robert Hoelzl, Barbara Bohle, Gordana Wozniak‐Knopp
Journal: Allergy (2023)

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Application of Artificial Intelligence to In Vitro Tumor Modeling and Characterization of the Tumor Microenvironment
Authors: Ren Yuan Lee, Yang Wu, Denise Goh, Verlyn Tan, Chan Way Ng, Jeffrey Chun Tatt Lim, Mai Chan Lau, Joe Poh Sheng Yeong
Journal: Advanced Healthcare Materials (2023)

Abstract In vitro tumor models have played vital roles in enhancing the understanding of the cellular and molecular composition of tumors, as well as their biochemical and biophysical characteristics. Advances in technology have enabled the evolution of tumor models from two‐dimensional cell cultures to three‐dimensional printed tumor models with increased levels of complexity and diverse output parameters. With the increase in complexity, the new generation of models is able to replicate the architecture and heterogeneity of the tumor microenvironment more realistically than their predecessors. In recent years, artificial intelligence (AI) has been used extensively in healthcare and research, and AI‐based tools have also been applied to the precise development of tumor models. The incorporation of AI facilitates the use of high‐throughput systems for real‐time monitoring of tumorigenesis and biophysical tumor properties, raising the possibility of using AI alongside tumor modeling for personalized medicine. Here, the integration of AI tools within tumor modeling is reviewed, including microfluidic devices and cancer‐on‐chip models.
Propensity score matching analysis of laparoscopic surgery vs. open approach in 4 297 adult patients with acute appendicitis, acute cholecystitis or gastrointestinal tract perforation: a prospective multicentre study of nationwide outcomes
Authors: Núria Lluís, Silvia Carbonell, Celia Villodre, Pedro Zapater, Miguel Cantó, Luís Mena, José M. Ramia, Félix Lluís
Journal: International Journal of Surgery (2023)

Previous studies indicated that laparoscopic surgery could improve postoperative outcomes in acute appendicitis, acute cholecystitis, perforated gastroduodenal ulcer, or acute diverticulitis, but some reported opposite results or differences in the magnitude of improvement. A contemporary analysis using propensity score matching that compares outcomes is lacking.Over a 6-month period, 38 centres (5% of all public hospitals) attending emergency general surgery patients on a 24 h, 7 days a week basis, enroled all consecutive adult patients who underwent laparoscopic surgery or open approach.The study included 2 645 patients with acute appendicitis [32 years (22-51), 44.3% women], 1 182 with acute cholecystitis [65 years (48-76); 46.7% women], and 470 with gastrointestinal tract perforation [65 years (50-76); 34% women]. After propensity score matching, hospital stays decreased in acute appendicitis [open, 2 days (2-4); lap, 2 days (1-4); P <0.001], acute cholecystitis [open, 7 days (4-12); lap, 4 days (3-6); P <0.001], and gastrointestinal tract perforation [open, 11 days (7-17); lap, 6 days (5-8.5); P <0.001]. A decrease in 30-day morbidity was observed in acute appendicitis (open, 15.7%; lap, 9.7%; P <0.001), acute cholecystitis (open, 41%; lap, 21.7%; P <0.001), and gastrointestinal tract perforation (open, 45.2%; lap, 23.5%; P <0.001). A decrease in 30-day mortality was found in acute cholecystitis (open, 8.8%; lap, 2.8%; P =0.013) and gastrointestinal tract perforation (open, 10.4%; lap, 1.7%; P =0.013).This clinically based, multicentre study suggests that an initial laparoscopic approach could be considered not only in patients with acute appendicitis or acute cholecystitis but also in patients with a perforation of the gastrointestinal tract.
VE303, a Defined Bacterial Consortium, for Prevention of Recurrent <i>Clostridioides difficile</i> Infection
Authors: Thomas Louie, Yoav Golan, Sahil Khanna, Dmitri Bobilev, Nathalie Erpelding, Candida Fratazzi, Meg Carini, Rajita Menon, Mary Ruisi, Jason M. Norman, Jeremiah J. Faith, Bernat Olle, Minran Li, Jeffrey L. Silber, Darrell S. Pardi
Journal: JAMA (2023)

The effect of rationally defined nonpathogenic, nontoxigenic, commensal strains of Clostridia on prevention of Clostridioides difficile infection (CDI) is unknown.To determine the efficacy of VE303, a defined bacterial consortium of 8 strains of commensal Clostridia, in adults at high risk for CDI recurrence. The primary objective was to determine the recommended VE303 dosing for a phase 3 trial.Phase 2, randomized, double-blind, placebo-controlled, dose-ranging study conducted from February 2019 to September 2021 at 27 sites in the US and Canada. The study included 79 participants aged 18 years or older who were diagnosed with laboratory-confirmed CDI with 1 or more prior CDI episodes in the last 6 months and those with primary CDI at high risk for recurrence (defined as aged ≥75 years or ≥65 years with ≥1 risk factors: creatinine clearance <60 mL/min/1.73 m2, proton pump inhibitor use, remote [>6 months earlier] CDI history).Participants were randomly assigned to high-dose VE303 (8.0 × 109 colony-forming units [CFUs]) (n = 30), low-dose VE303 (1.6 × 109 CFUs) (n = 27), or placebo capsules (n = 22) orally once daily for 14 days.The primary efficacy end point was the proportion of participants with CDI recurrence at 8 weeks using a combined clinical and laboratory definition. The primary efficacy end point was analyzed in 3 prespecified analyses, using successively broader definitions for an on-study CDI recurrence: (1) diarrhea consistent with CDI plus a toxin-positive stool sample; (2) diarrhea consistent with CDI plus a toxin-positive, polymerase chain reaction-positive, or toxigenic culture-positive stool sample; and (3) diarrhea consistent with CDI plus laboratory confirmation or (in the absence of a stool sample) treatment with a CDI-targeted antibiotic.Baseline characteristics were similar across the high-dose VE303 (n = 29; 1 additional participant excluded from efficacy analysis), low-dose VE303 (n = 27), and placebo (n = 22) groups. The participants' median age was 63.5 years (range, 24-96); 70.5% were female; and 1.3% were Asian, 1.3% Black, 2.6% Hispanic, and 96.2% White. CDI recurrence rates through week 8 (using the efficacy analysis 3 definition) were 13.8% (4/29) for high-dose VE303, 37.0% (10/27) for low-dose VE303, and 45.5% (10/22) for placebo (P = .006, high-dose VE303 vs placebo).Among adults with laboratory-confirmed CDI with 1 or more prior CDI episodes in the last 6 months and those with primary CDI at high risk for recurrence, high-dose VE303 prevented recurrent CDI compared with placebo. A larger, phase 3 study is needed to confirm these findings.ClinicalTrials.gov Identifier: NCT03788434.
Tuberous Sclerosis Complex Kidney Lesion Pathogenesis: A Developmental Perspective
Authors: Adam Pietrobon, William L. Stanford
Journal: Journal of the American Society of Nephrology (2023)

The phenotypic diversity of tuberous sclerosis complex (TSC) kidney pathology is enigmatic. Despite a well-established monogenic etiology, an incomplete understanding of lesion pathogenesis persists. In this review, we explore the question: How do TSC kidney lesions arise? We appraise literature findings in the context of mutational timing and cell-of-origin. Through a developmental lens, we integrate the critical results from clinical studies, human specimens, and genetic animal models. We also review novel insights gleaned from emerging organoid and single-cell sequencing technologies. We present a new model of pathogenesis which posits a phenotypic continuum, whereby lesions arise by mutagenesis during development from variably timed second-hit events. This model can serve as a conceptual framework for testing hypotheses of TSC lesion pathogenesis, both in the kidney and in other affected tissues.
Elacestrant: First Approval
Authors: Sheridan M. Hoy
Journal: Drugs (2023)

Elacestrant (ORSERDU™) is an orally available selective estrogen receptor degrader (SERD) being developed by Stemline Therapeutics, a subsidiary of Menarini Group, for the treatment of estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. In January 2023, elacestrant received its first approval for the treatment of postmenopausal women or adult men with ER-positive, HER2-negative, estrogen receptor 1 (ESR1)-mutated (as determined by a US FDA-approved test) advanced or metastatic breast cancer with disease progression following ≥ 1 line of endocrine therapy in the USA. A regulatory assessment of elacestrant for the treatment of ER-positive, HER2-negative advanced or metastatic breast cancer is currently underway in the EU. Development of elacestrant for the treatment of vasomotor symptoms has been discontinued. This article summarizes the milestones in the development of elacestrant leading to this first approval for this indication.